The Journal of Bone and Joint Surgery (American). 2008;90:111-119.
doi:10.2106/JBJS.G.01572
© 2008 The Journal of Bone and Joint Surgery, Inc.
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Cellular Strategies for Enhancement of Fracture Repair

Thomas E. Patterson, PhD, Ken Kumagai, MD, PhD, Linda Griffith, PhD and George F. Muschler, MD

Corresponding author:
George F. Muschler, MD
Departments of Orthopaedic Surgery and Biomedical Engineering (ND-20), Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195.
E-mail address: muschlg{at}ccf.org

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the National Institutes of Health (the National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS] and the National Institute of General Medical Sciences [NIGMS]) and Therics, Inc. One or more of the authors, or a member of his or her immediate family, received, in any one year, payments or other benefits or a commitment or agreement to provide such benefits from commercial entities in excess of $10,000 (DePuy, Synthes, and Therics, Inc.) and less than $10,000 (Orthofix). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Tissue engineering seeks to translate scientific knowledge into tangible products to advance the repair, replacement, or regeneration of organs and tissues. Current tissue engineering strategies have progressed recently from a historical approach that is based primarily on biomaterials to a cell and tissue-based approach that includes understanding of cell-sourcing and bioactive stimuli. New options include methods for harvest and transplantation of tissue-forming cells, bioactive matrix materials that act as tissue scaffolds, and delivery of bioactive molecules within scaffolds. These strategies are already benefiting patients, and they place increasing demands on orthopaedic surgeons to have a solid foundation in the contemporary concepts and principles of cell-based tissue engineering.

Essentially all orthopaedic tissue engineering strategies can be distilled to a strategy or combination of strategies that seek to increase the number or relative performance of bone-forming cells. The global term connective tissue progenitors has been used to define the heterogeneous populations of stem and progenitor cells that are found in native tissue and that are capable of differentiating into one or more connective tissue phenotypes. These stem or progenitor populations are found in various tissue sources, with varying degrees of ability to differentiate along connective tissue lineages. Available cell-based strategies include targeting local cells with use of scaffolds or bioactive factors, or transplantation of autogenous connective tissue progenitor cells derived from bone marrow or other tissues, with or without processing to change their concentration or prevalence. The future may include means of homing circulating connective tissue progenitor cells with use of intrinsic chemokine systems, or modifying the biological performance of connective tissue progenitor cells by means of genetic modifications.


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